Magnesium is the fourth most abundant mineral in the human body and plays multiple roles in maintaining good health. At the molecular level, magnesium is a cofactor for over 300 enzymes responsible for some of the most important biological activities in mammals, including humans. In living cells, magnesium is involved in the homeostasis of other minerals, such as sodium, potassium and calcium, and the formation, transfer, storage and utilization of adenosine triphosphate (ATP), a principal source of energy in living cells. In the human body, magnesium is involved in the maintenance of normal muscle and nerve function, heart rhythm, bone strength, and immune system health. Magnesium is also involved in the regulation of blood sugar levels and the promotion of normal blood pressure.
Magnesium deficit has been associated with several diseases, including hypertension, atherosclerosis, arrhythmia, diabetes, and metabolic syndromes. In addition, magnesium deficit accelerates cell-aging processes (Killilea D W, Ames B N. Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts. Proc Natl Acad Sci USA. 2008 Apr. 15; 105:5768-73). Magnesium is also important for brain function. For example, magnesium deficit is implicated in attention deficit hyperactivity disorder (Kozielec T, Starobrat-Hermelin B. Magnes Res. 1997 June; 10:143-8; Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali J P. Magnes Res. 2006 March; 19:46-52), affective disorders (Murck H. Nutritional neuroscience. 2002 December; 5:375-89), Alzheimer's disease (Andrasi E, Pali N, Molnar Z, Kosel S. J Alzheimers Dis. 2005 August; 7:273-84; Cilliler A E, Ozturk S, Ozbakir S. Gerontology. 2007 Nov. 8; 53:419-22; Lemke M R. Biol Psychiatry. 1995 Mar. 1; 37:341-3), migraine (Ramadan N M, Halvorson H, Vande-Linde A, Levine S R, Helpern J A, Welch K M. Headache. 1989 October; 29:590-3; Facchinetti F, Sances G, Borella P, Genazzani A R, Nappi G. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache. 1991 May; 31:298-301), and Autism (Martineau J, Barthelemy C, Garreau B, Lelord G. Biol Psychiatry. 1985 May; 20:467-78; Pfeiffer S I, Norton J, Nelson L, Shott S. J Autism Dev Disord. 1995 October; 25:481-93; Strambi M, Longini M, Hayek J, Berni S, Macucci F, Scalacci E, Vezzosi P., Biol Trace Elem Res. 2006 February; 109:97-104).
Recently, it has been found that elevation of extracellular magnesium leads to a significant enhancement of synaptic plasticity and synaptic density in cultured hippocampal neurons (Slutsky I, Sadeghpour S, Li B, Liu G. Neuron. 2004 Dec. 2; 44:835-49). The synaptic network is believed to be involved in organization of neural circuits during early development and in learning and memory processes. Indeed, in patients with Alzheimer's disease, there is a strong inverse correlation between the number of synapses and the degree of cognitive impairment (Terry R D, Masliah E, Salmon D P, Butters N, DeTeresa R, Hill R, Hansen L A, Katzman R. Ann Neurol. 1991 October; 30:572-80; Selkoe D J. Science. 2002 Oct. 25; 298:789-91). During normal aging, memory decline also correlates with synaptic loss (Terry R D, Masliah E, Salmon D P, Butters N, DeTeresa R, Hill R, Hansen L A, Katzman R. Ann Neurol. 1991 October; 30:572-80). Interestingly, brain magnesium contents in AD patients (Andrasi E, Pali N, Molnar Z, Kosel S. J Alzheimers Dis. 2005 August; 7:273-84; Cilliler A E, Ozturk S, Ozbakir S. Gerontology. 2007 Nov. 8; 53:419-22) are lower than normal subjects. Elevation of brain magnesium might be beneficial for prevention of synapse loss and amelioration of memory decline during aging and the pathological processes of AD.
Despite the important physiological role of magnesium, people may not consume enough magnesium in their diets. In a national sample of the United States, the mean value of daily magnesium between the ages of 20-30 is ˜300 mg for white and ˜250 mg for black males. This daily intake declines, at ages above 70 years, to ˜200 mg as a result of reduced food consumption. On the other hand, the recommended daily allowance (RDA) for males is 420 mg/day. Therefore, it is likely that the majority of the American male population has magnesium deficit, particularly during aging. A similar degree of deficit also occurs in American female population (Ford E S, Mokdad A H. J. Nutr. 2003 September; 133:2879-82). Based on this study, most of the American population needs to supplement their diet with an additional ˜200 mg/day of magnesium. Interestingly, magnesium contained in food provides relatively high absorption rate magnesium (˜50%), which may suggest that ˜100 mg/day magnesium remains needed to be absorbed into the body. In general, most commercially available magnesium preparations have a magnesium absorption rate <˜40%. For example, magnesium oxide, which is perhaps the most widely used magnesium supplement, has a magnesium absorption rate of only about 4% (Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnes Res. 2001 December; 14:257-62)). The present invention provides controlled release magnesium compositions for use as a magnesium dietary supplement.